Polyclonal activation or specific antigenic stimulation of lymphocytes initiates a complex series of events, including the elaboration of the anti-viral protein, immune interferon. This mediator is known to be a product of thymus-derived lymphocytes (T cells) of mouse or human origin. The report of interferon detected in supernatants of cultures comprised of highly enriched proportions of human non-thymus derived lymphocytes (B cells), suggests that activated murine B cells might also elaborate interferon. The present proposal will investigate the production of immune interferon by murine B cell subsets in response to stimulation with mitogens or antigens. Additionally, the murine T cell subset responsible for interferon production will be characterized; and the extent and genetic requirements of macrophage participation will be studied. Murine plasmacytomas and thymomas will be examined as possible abundant sources of T cell or B cell-derived immune interferon preparations. Attempts will be made to partially purify the interferon from such preparations. Both crude and such partially purified interferon preparations will be tested for their effects on the immune response both in assays involving the in vitro proliferative response to mitogen or antigen stimulation and in vitro antibody response. The cell targets of the interferon immunoregulatory activity in the immune response will be characterized by pretreating isolated macrophage T cell or B cells populations with interferon prior to recombining them in cultures for an immune response and by performing comparative limiting dilution analysis of cells cultured in the presence and absence of interferon.